Exclusive Human-milk in Preterm NEOnates and Early VASCular Aging Risk Factors (NEOVASC) (NEOVASC)

Effects of an Exclusive Human-milk Diet in Preterm NEOnates on Early VASCular Aging Risk Factors (NEOVASC)

Early vascular aging has its origins in fetal and neonatal life. The NEOVASC clinical trial aims to determine the effects of an exclusive human milk diet in extremely preterm infants on long-term cardiovascular health.

Study Overview

• Status: Recruiting
• Conditions: Prematurity; Vascular Aging
• Intervention / Treatment: Dietary supplement: Humavant

Detailed Description

Early vascular aging has its origins in fetal and neonatal life. This early period of life plays an important role in the development of obesity, high blood pressure, abnormalities in lipid metabolism and non-insulin dependent diabetes. Increased cardiovascular risk in formerly preterm infants constitutes a health problem of steadily growing relevance. Emerging evidence suggests that human milk feeding has substantial benefits to the health of all infants, especially for those born prematurely. Unfortunately, human milk alone does not provide sufficient concentrations of nutrients, especially calcium, phosphorus, protein, and fat needed for these infants to grow satisfactorily. For that purpose, fortifiers are used to help increase the nutritional value of human milk.

The NEOVASC study is a multicentric, prospective, randomized, controlled, open and parallel group clinical trial. A total of 200 extremely preterm infants and 100 term infants are recruited for the test and control group, respectively. Infants in the test group (i.e., premature neonates) are randomized to either:

1. An exclusive human milk diet which contains mother's milk or pasteurized donor human milk and a human milk fortifier until 36 weeks of gestation; OR
2. Human milk (as long as available) and a human milk fortifier (as long as human milk is available) until a maximum of 32 weeks of gestation and thereafter human milk with a bovine-based fortifier or preterm formula.

After 36 weeks of gestation, human milk with a bovine-based fortifier or preterm formula is used in both groups. As a control group, term-born age-matched controls are included. Participants within this control group are not enrolled at the time of birth but instead recruited in various kindergartens at the age of five. Therefore, data from birth is taken from the mother-child-booklet, which contains clinical records about the pregnancy, birth and early life of children born in Austria. The total study duration is scheduled for 96 months with a recruitment phase of 36 months. Follow-up visits are planned at one, two and five years of age for the test group.

The purpose of the NEOVASC clinical trial is to characterize early life stressors by assessing the effects of a physiological (i.e., human milk-based) nutrition in extremely preterm infants during the vulnerable preterm period on the risk of metabolic and vascular complications in later life. Outcomes include predictors and intermediate components of cardiovascular disease.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ursula Kiechl-Kohlendorfer, MD, MSc; Phone Number: +43 512 504 27309; Email: ursula.kohlendorfer@i-med.ac.at
• Study Contact Backup: Name: Wolfgang Mitterer, MD; Phone Number: +43 670 2021490; Email: wolfgang.mitterer@student.i-med.ac.at

Study Locations

• Austria
  • Tyrol
    • Innsbruck, Tyrol, Austria, A-6020
      • Recruiting
      • Medical University of Innsbruck
      • Contact: Ursula Kiechl-Kohlendorfer, MD, MSc; Phone Number: +43 512 504 27309; Email: ursula.kohlendorfer@i-med.ac.at
      • Contact: Wolfgang Mitterer, MD; Email: wolfgang.mitterer@student.i-med.ac.at
      • Principal Investigator: Christoph Binder, MD
      • Principal Investigator: Martin Wald, MD
      • Principal Investigator: Burkhard Simma, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 5 years (Child)
• Accepts Healthy Volunteers: No

Description

Preterm-born group:

Inclusion Criteria:

1. Extremely preterm infants with a birth weight of 500-1250g.
2. Feeding is NPO or exclusive human milk prior to enrollment.
3. Parent(s) willing to sign informed consent.-

Exclusion Criteria:

1. Infants with a birth weight <500g or >1250g
2. Subjects diagnosed with inborn errors of metabolism such as galactosemia, phenylketonuria
3. Subjects who have not been NPO or fed exclusive human milk diet prior to enrollment.
4. Presence of major congenital malformation.
5. Presence of intestinal perforation or Stage 2 Necrotizing enterocolitis prior to enrollment.
6. Parent(s) not willing to sign informed consent.
7. Unable to participate for any reason based on the decision of the study investigator (e.g. unlikely to survive the study period).

Term-born group:

Inclusion criteria

1. Term-born children with an adequate birth weight
2. Parent(s) willing to sign informed consent

Exclusion criteria

1. Subjects with acute or chronic illness
2. Parent(s) not willing to sign informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Randomized study product group; receiving study product (human milk fortifier "Humavant") until a gestational age of 36 weeks	Dietary supplement: Humavant; Premature infants are randomized to either: An exclusive human milk diet which contains mother's milk or pasteurized donor human milk and the human milk fortifier until 36 weeks of gestation; OR; Human milk (as long as available) and the human milk fortifier (as long as human milk is available) until a maximum of 32 weeks of gestation and thereafter human milk with a bovine-based fortifier or preterm formula. After 36 weeks of gestation, human milk with a bovine-based fortifier or preterm formula is used in both groups. As a control group, term-born age-matched controls are included.
Active Comparator: Randomized control group; receiving study product until a gestational age of 32 weeks and reference product (bovine based fortifier or bovine formula) after 32 weeks of gestation	Dietary supplement: Humavant; Premature infants are randomized to either: An exclusive human milk diet which contains mother's milk or pasteurized donor human milk and the human milk fortifier until 36 weeks of gestation; OR; Human milk (as long as available) and the human milk fortifier (as long as human milk is available) until a maximum of 32 weeks of gestation and thereafter human milk with a bovine-based fortifier or preterm formula. After 36 weeks of gestation, human milk with a bovine-based fortifier or preterm formula is used in both groups. As a control group, term-born age-matched controls are included.
No Intervention: Term control group; Term-born controls as a reference group for outcome parameters

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting blood glucose	Primary outcome is the difference in fasting blood glucose at five years of age	"First day of life" up to "five years"
Blood pressure	Primary outcome is the difference in blood pressure at five years of age	"First day of life" up to "five years"
Distensibility of aorta	Primary outcome is the difference in the distensibility of the descending aorta using validated echocardiographic protocols at five years of age	"First day of life" up to "five years"

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting blood glucose	Secondary outcome is fasting glucose at a corrected age of one and two years.	"First day of life" up to "24 months"
Blood pressure	Secondary outcome is blood pressure at a corrected age of one and two years.	"First day of life" up to "24 months"
BMI	Secondary outcome is BMI at five years of age, weight in kilograms and height in meters will be combined to report BMI in kg/m2	"First day of life" up to "five years"
Insulin sensitivity	Secondary outcome is insulin sensitivity at five years of age	"First day of life" up to "five years"
Lipid profile	Secondary outcome is lipid profile at five years of age	"First day of life" up to "five years"

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting blood glucose	Difference in fasting blood glucose between preterm- and term-born children at five years of age	"five years of age"
Blood pressure	Difference in blood pressure between preterm- and term-born children at five years of age	"five years of age"
Distensibility of the descending aorta	Difference in the distensibility of the descending aorta between preterm- and term-born children using validated echocardiographic protocols at five years of age Results will be compared to results of term-born children	"five years of age"
BMI	Difference in BMI between preterm- and term-born children at five years of age, weight in kilograms and height in meters will be combined to report BMI in kg/m2	"five years of age"
Insulin sensitivity	Difference in insulin sensitivity between preterm- and term-born children at five years of age	"five years of age"
Lipid profile	Difference in lipid profile between preterm- and term-born children at five years of age	"five years of age"

Collaborators and Investigators

• Sponsor: Prolacta Bioscience
• Collaborators: Medical University of Vienna; Paracelsus Medical University; Federal University Teaching Hospital, Feldkirch, Austria
• Investigators: Principal Investigator: Ursula Kiechl-Kohlendorfer, MD, MSc, Medical University of Innsbruck

Publications and helpful links

General Publications

• Mitterer W, Binder C, Blassnig-Ezeh A, Auer-Hackenberg L, Berger A, Simma B, Wald M, Lee M, Kiechl-Kohlendorfer U. Effects of an exclusive human-milk diet in preterm neonates on early vascular aging risk factors (NEOVASC): study protocol for a multicentric, prospective, randomized, controlled, open, and parallel group clinical trial. Trials. 2021 Jul 31;22(1):509. doi: 10.1186/s13063-021-05445-9.

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2020
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: May 26, 2020
• First Submitted That Met QC Criteria: May 30, 2020
• First Posted (Actual): June 4, 2020

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth
• Other Study ID Numbers: NEOVASC; 868624 (Other Grant/Funding Number: Austrian Research Promotion Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No